ChemicalBook CAS DataBase List 4-CHLORO (1H)INDAZOLE

4-CHLORO (1H)INDAZOLE synthesis

7synthesis methods

Product Name:4-CHLORO (1H)INDAZOLE
CAS Number:13096-96-3
Molecular formula:C7H5ClN2
Molecular Weight:152.58

87-60-5 Synthesis

87-60-5
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$8.00/25g

13096-96-3
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$15.00/250mg

Yield: 100%

Reaction Conditions:

Stage #1:3-chloro-2-methylbenzenamine with potassium acetate;acetic anhydride in chloroform at 0 - 25; for 1.03333 h;
Stage #2: with isopentyl nitrite in chloroform at 60;

Steps:

10.A.A
Example 10; l-(Tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl- 1,3,2- dioxaborolan-2-yl)-lH-indazole 62 (Route A)[00252] Step A: Preparation of 4-chloro-lH-indazole: To a 250 ml flask with stirbar was added 2-methyl-3-chloroaniline (8.4 ml, 9.95 g, 70.6 mmol), potassium acetate (8.3 g, 84.7 mmol) and chloroform (120 ml). This mixture was cooled to 0 ⁰C with stirring. To the cooled mixture was added acetic anhydride (20.0 ml, 212 mmol) drop wise over 2 minutes. The reaction mixture was warmed to 25 ⁰C and stirred for 1 hour. At this point, the reaction was heated to 60 ⁰C. Isoamyl nitrite (18.9 ml, 141 mmol) was added and the reaction was stirred overnight at 60 ⁰C. Once complete, water (75 ml) and THF (150 ml) were added and the reaction was cooled to 0 ⁰C. LiOH (20.7 g, 494 mmol) was added and the reaction was stirred at0 ⁰C for 3 hours. Water (200 ml) was added and the product was extracted with EtOAc (300 ml, 100 ml). The organic layers were combined, dried with MgSO₄ and concentrated in vacuo to yield 11.07 g 4-chloro-lH-indazole (100%) as an orange solid. ¹H NMR (400 MHz, CDCl₃) δ 8.18 (d, J= 1 Hz, IH), 7.33 (d, J= 8 Hz IH), 7.31 (t, J= 7 Hz, IH), 7.17 (dd, J= 7 Hz, 1 Hz IH). LCMS (ESI pos) m/e 153 (M+l).

References:

GENENTECH, INC.;F. HOFFMANN - LA ROCHE AG WO2009/42607, 2009, A1 Location in patent:Page/Page column 74

387-45-1 Synthesis